High-Tc Ferromagnetic Semiconductor in Thinned 3D Ising Ferromagnetic Metal Fe3GaTe2.

Emergent phenomena in exfoliated layered transition metal compounds have attracted much attention in the past several years. Especially, pursuing a ferromagnetic insulator is one of the exciting goals for stimulating a high-performance magnetoelectrical device. Here, we report the transition from a metallic to high-Tc semiconductor-like ferromagnet in thinned Fe3GaTe2, accompanied with competition among various magnetic interactions. As evidenced by critical exponents, Fe3GaTe2 is the first layered ferromagnet described by a 3D Ising model coupled with long-range interactions. An extra magnetic phase from competition between ferromagnetism and antiferromagnetism emerges at a low field below Tc. Upon reducing thickness, the Curie temperature (Tc) monotonically decreases from 342 K for bulk to 200 K for 1-3 nm flakes, which is the highest Tc reported as far as we know. Furthermore, a semiconductor-like behavior has been observed in such 1-3 nm flakes. Our results highlight the importance of Fe3GaTe2 in searching for ferromagnetic insulators, which may benefit spintronic device fabrication.

Amino acid metabolic reprogramming in the tumor microenvironment and its implication for cancer therapy.

Amino acids are essential building blocks for proteins, crucial energy sources for cell survival, and key signaling molecules supporting the resistant growth of tumor cells. In tumor cells, amino acid metabolic reprogramming is characterized by the enhanced uptake of amino acids as well as their aberrant synthesis, breakdown, and transport, leading to immune evasion and malignant progression of tumor cells. This article reviews the altered amino acid metabolism in tumor cells and its impact on tumor microenvironment, and also provides an overview of the current clinical applications of amino acid metabolism. Innovative drugs targeting amino acid metabolism hold great promise for precision and personalized cancer therapy.

Overexpression of rice OsNRT1.1A/OsNPF6.3 enhanced the nitrogen use efficiency of wheat under low nitrogen conditions.

MAIN CONCLUSION: Overexpression of OsNRT1.1A promotes early heading and increases the tolerance in wheat under nitrogen deficiency conditions. The application of inorganic nitrogen (N) fertilizers is a major driving force for crop yield improvement. However, the overuse of fertilizers significantly raises production costs and leads to environmental problems, making it critical to enhance crop nitrogen use efficiency (NUE) for the sake of sustainable agriculture. In this study, we created a series of transgenic wheat lines carrying the rice OsNRT1.1A gene, which encodes a nitrate transporter, to investigate its possible application in improving NUE in wheat. The transgenic wheat exhibited traits such as early maturation that were highly consistent with the overexpression of OsNRT1.1A in Arabidopsis and rice. However, we also observed that overexpression of the OsNRT1.1A gene in wheat can facilitate the growth of roots under low N conditions but has no effect on other aspects of growth and development under normal N conditions. Thus, it may lead to the improvement of wheat low N tolerance,which is different from the effects reported in other plants. A field trial analysis showed that transgenic wheat exhibited increased grain yield per plant under low N conditions. Moreover, transcriptome analysis indicated that OsNRT1.1A increased the expression levels of N uptake and utilization genes in wheat, thereby promoting plant growth under low N conditions. Taken together, our results indicated that OsNRT1.1A plays an important role in improving NUE in wheat with low N availability.

The auxin response factor TaARF15-A1 negatively regulates senescence in common wheat (Triticum aestivum L.).

Auxin plays an important role in regulating leaf senescence. Auxin response factors (ARFs) are crucial components of the auxin signaling pathway; however, their roles in leaf senescence in cereal crops are unknown. In this study, we identified TaARF15-A1 as a negative regulator of senescence in wheat (Triticum aestivum L.) by analyzing TaARF15-A1 overexpression (OE) and RNA interference lines and CRISPR/Cas9-based arf15 mutants. OE of TaARF15-A1 delayed senescence, whereas knockdown lines and knockout mutants showed accelerated leaf senescence and grain ripening. RNA-seq analysis revealed that TaARF15-A1 delays leaf senescence by negatively regulating senescence-promoting processes and positively modulating senescence-delaying genes including senescence-associated phytohormone biosynthesis and metabolism genes as well as transcription factors (TFs). We also demonstrated that TaARF15-A1 physically interacts with TaMYC2, a core jasmonic acid (JA) signaling TF that positively modulates wheat senescence. Furthermore, TaARF15-A1 suppressed the expression of TaNAM-1 (TaNAM-A1 and TaNAM-D1) via protein-protein interaction and competition with TaMYC2 for binding to its promoter to regulate senescence. Finally, we identified two haplotypes of TaARF15-A1 in global wheat collections. Association analysis revealed that TaARF15-A1-HapI has undergone strong selection during wheat breeding in China, likely owing to its earlier maturity. Thus, we identify TaARF15-A1 as a negative regulator of senescence in common wheat and present another perspective on the crosstalk between auxin and JA signaling pathways in regulating plant senescence.

Gustative Roussy Immune Score is a Predictor for Major Pathological Response in Rectal Cancer: A Result from the Preoperative Intraarterial Chemoembolization Combined with Radiotherapy (PCAR) Study.

Despite the emergence of various treatment strategies for rectal cancer based on neoadjuvant chemoradiotherapy, there is currently a lack of reliable biomarkers to determine which patients will respond well to neoadjuvant chemoradiotherapy. Through collecting hematological and biochemical parameters data of patients prior to receiving neoadjuvant chemoradiotherapy, we evaluated the predictive value of systemic inflammatory indices for pathological response and prognosis in rectal cancer patients. We found that baseline GRIm-Score was an independent predictor for MPR in rectal cancer patients. However, no association was observed between several commonly systemic inflammation indices and long-term outcome.

Regulation of Immune Inflammation and Promotion of Periodontal Bone Regeneration by Irisin-Loaded Bioactive Glass Nanoparticles.

Clinical solutions of bone defects caused by periodontitis involve surgical treatment and subsequent anti-infection treatment using antibiotics. Such a strategy faces a key challenge in that the excessive host immune response results in the damage of periodontal tissues. Consequently, it is of great importance to develop novel periodontitis treatment that allows the regulation of the host immune response and promotes the generation of periodontal tissues. Irisin has a good bone regeneration ability and could reduce the inflammatory reaction by regulating the differentiation of macrophages. In this study, we loaded irisin onto bioactive glass nanoparticles (BGNs) to prepare a composite, irisin-BGNs (IR-BGNs) with anti-inflammatory, bacteriostatic, and tissue regeneration functions, providing a novel idea for the design of ideal materials for repairing oral tissue defects caused by periodontitis. We also verified that the IR-BGNs had better anti-inflammatory properties on RAW264.7 cells compared to irisin and BGNs alone. Strikingly, when hPDLCs were stimulated with IR-BGNs, they exhibited increased expression of markers linked to osteogenesis, ALP activity, and mineralization ability in comparison to the negative control. Furthermore, on the basis of RNA sequencing results, we validated that the p38 pathway can contribute to the osteogenic differentiation of the IR-BGNs. This work may offer new thoughts on the design of ideal materials for repairing oral tissue defects.

Quorum Quenching in Membrane Bioreactors for Fouling Retardation: Complexity Provides Opportunities.

The occurrence of biofouling restricts the widespread application of membrane bioreactors (MBRs) in wastewater treatment. Regulation of quorum sensing (QS) is a promising approach to control biofouling in MBRs, yet the underlying mechanisms are complex and remain to be illustrated. A fundamental understanding of the relationship between QS and membrane biofouling in MBRs is lacking, which hampers the development and application of quorum quenching (QQ) techniques in MBRs (QQMBRs). While many QQ microorganisms have been isolated thus far, critical criteria for selecting desirable QQ microorganisms are still missing. Furthermore, there are inconsistent results regarding the QQ lifecycle and the effects of QQ on the physicochemical characteristics and microbial communities of the mixed liquor and biofouling assemblages in QQMBRs, which might result in unreliable and inefficient QQ applications. This review aims to comprehensively summarize timely QQ research and highlight the important yet often ignored perspectives of QQ for biofouling control in MBRs. We consider what this "information" can and cannot tell us and explore its values in addressing specific and important questions in QQMBRs. Herein, we first examine current analytical methods of QS signals and discuss the critical roles of QS in fouling-forming microorganisms in MBRs, which are the cornerstones for the development of QQ technologies. To achieve targeting QQ strategies in MBRs, we propose the substrate specificity and degradation capability of isolated QQ microorganisms and the surface area and pore structures of QQ media as the critical criteria to select desirable functional microbes and media, respectively. To validate the biofouling retardation efficiency, we further specify the QQ effects on the physicochemical properties, microbial community composition, and succession of mixed liquor and biofouling assemblages in MBRs. Finally, we provide scale-up considerations of QQMBRs in terms of the debated QQ lifecycle, practical synergistic strategies, and the potential cost savings of MBRs. This review presents the limitations of classic QS/QQ hypotheses in MBRs, advances the understanding of the role of QS/QQ in biofouling development/retardation in MBRs, and builds a bridge between the fundamental understandings and practical applications of QQ technology.

Effect of ticagrelor versus clopidogrel after implantation of drug-eluting stents guided by either intravascular ultrasound or angiography in patients with acute coronary syndrome-propensity score matching analysis.

BACKGROUND: The effect of different dual antiplatelet therapies on thrombotic events on the background of intravascular ultrasound (IVUS) guidance is unclear. We investigated whether ticagrelor can provide any additional benefit to clopidogrel in reducing thrombotic events in acute coronary syndrome (ACS) treated with drug- eluting stent (DES), when guided by IVUS or not. METHODS: A total of 5,666 ACS patients who underwent DES implantation and who were discharged on dual antiplatelet therapy were enrolled and grouped according to the use of IVUS or not. Each group was subdivided into two subgroups according to the type of P2Y12 inhibitor used after discharge. Propensity score matching (PSM) was used between the IVUS and no-IVUS groups. Covariate adjustment of Cox proportional hazards model was used between the ticagrelor and clopidogrel groups. Thrombotic event at 12 months was compared in groups separately. RESULTS: After PSM, 12-month follow-up data were available for 1,174 patients. Major adverse cardiac events (MACE) were less frequent in the IVUS-guided group (2.2% vs. 4.3%, P = 0.081) with a trend toward statistical significance. Comparison of antiplatelet regimens revealed significantly fewer major adverse cardiac and cerebrovascular events (MACCE) with ticagrelor in the entire PSM cohort and angiography-guided subgroup (2.9% vs. 5.7%, P = 0.035; 3.1% vs. 6.4%, P = 0.020, respectively). Among patients in the IVUS-guided group the outcome was comparable (2.5% vs. 4.4%, P = 0.312). Ticagrelor was associated with increasing bleeding incidence in the entire PSM cohort (1.3% vs. 3.3%, P = 0.030), mainly due to Bleeding Academic Research Consortium type 2 bleeding (0.7% vs. 2.6%, P = 0.010). The results were consistent after covariate adjustment of Cox proportional hazards model. CONCLUSION: The comparison of ischemic benefit between ticagrelor and clopidogrel was similar in patients receiving IVUS guidance during stent implantation, probably due to the precise implantation of IVUS. Multicenter, randomized studies should be performed to validate this conclusion.

Natural anti-neuroinflammatory inhibitors in vitro and in vivo from Aglaia odorata.

Fifty compounds including seven undescribed (1, 13, 18-20, 30, 31) and forty-three known (2-12, 14-17, 21-29, 32-50) ones were isolated from the extract of the twigs and leaves of Aglaia odorata with anti-neuroinflammatory activities. Their structures were determined by a combination of spectral analysis and calculated spectra (ECD and NMR). Among them, compounds 13-25 were found to possess tertiary amide bonds, with compounds 16, 17, and 19-21 existing detectable cis/trans mixtures in 1H NMR spectrum measured in CDCl3. Specifically, the analysis of the cis-trans isomerization equilibrium of tertiary amides in compounds 19-24 was conducted using NMR spectroscopy and quantum chemical calculations. Bioactivity evaluation showed that the cyclopenta[b]benzofuran derivatives (2-6, 8, 10, 12) could inhibit nitric oxide production at the nanomolar concentration (IC50 values ranging from 2 to 100 nM) in lipopolysaccharide-induced BV-2 cells, which were 413-20670 times greater than that of the positive drug (minocycline, IC50 = 41.34 µM). The cyclopenta[bc]benzopyran derivatives (13-16), diterpenoids (30-35), lignan (40), and flavonoids (45, 47, 49, 50) also demonstrated significant inhibitory activities with IC50 values ranging from 1.74 to 38.44 µM. Furthermore, the in vivo anti-neuroinflammatory effect of rocaglaol (12) was evaluated via immunofluorescence, qRT-PCR, and western blot assays in the LPS-treated mice model. The results showed that rocaglaol (12) attenuated the activation of microglia and decreased the mRNA expression of iNOS, TNF-α, IL-1ß, and IL-6 in the cortex and hippocampus of mice. The mechanistic study suggested that rocaglaol might inhibit the activation of the NF-κB signaling pathway to relieve the neuroinflammatory response.

Impact of operative time on textbook outcome after minimally invasive esophagectomy, a risk-adjusted analysis from a high-volume center.

BACKGROUND: We aimed to study the impact of operative time on textbook outcome (TO), especially postoperative complications and length of postoperative stay in minimally invasive esophagectomy. METHODS: Patients undergoing esophagectomy for curative intent within a prospectively maintained database from 2016 to 2022 were retrieved. Relationships between operative time and outcomes were quantified using multivariable mixed-effects models with medical teams random effects. A restricted cubic spline (RCS) plotting was used to characterize correlation between operative time and the odds for achieving TO. RESULTS: Data of 2210 patients were examined. Median operative time was 270 mins (interquartile range, 233-313) for all cases. Overall, 902 patients (40.8%) achieved TO. Among non-TO patients, 226 patients (10.2%) had a major complication (grade ≥ III), 433 patients (19.6%) stayed postoperatively longer than 14 days. Multivariable analysis revealed operative time was associated with higher odds of major complications (odds ratio 1.005, P < 0.001) and prolonged postoperative stay (≥ 14 days) (odds ratio 1.003, P = 0.006). The relationship between operative time and TO exhibited an inverse-U shape, with 298 mins identified as the tipping point for the highest odds of achieving TO. CONCLUSIONS: Longer operative time displayed an adverse influence on postoperative morbidity and increased lengths of postoperative stay. In the present study, the TO displayed an inverse U-shaped correlation with operative time, with a significant peak at 298 mins. Potential factors contributing to prolonged operative time may potentiate targets for quality metrics and risk-adjustment process.

Dynamic hydrogel-metal-organic framework system promotes bone regeneration in periodontitis through controlled drug delivery.

Periodontitis is a prevalent chronic inflammatory disease, which leads to gradual degradation of alveolar bone. The challenges persist in achieving effective alveolar bone repair due to the unique bacterial microenvironment's impact on immune responses. This study explores a novel approach utilizing Metal-Organic Frameworks (MOFs) (comprising magnesium and gallic acid) for promoting bone regeneration in periodontitis, which focuses on the physiological roles of magnesium ions in bone repair and gallic acid's antioxidant and immunomodulatory properties. However, the dynamic oral environment and irregular periodontal pockets pose challenges for sustained drug delivery. A smart responsive hydrogel system, integrating Carboxymethyl Chitosan (CMCS), Dextran (DEX) and 4-formylphenylboronic acid (4-FPBA) was designed to address this problem. The injectable self-healing hydrogel forms a dual-crosslinked network, incorporating the MOF and rendering its on-demand release sensitive to reactive oxygen species (ROS) levels and pH levels of periodontitis. We seek to analyze the hydrogel's synergistic effects with MOFs in antibacterial functions, immunomodulation and promotion of bone regeneration in periodontitis. In vivo and in vitro experiment validated the system's efficacy in inhibiting inflammation-related genes and proteins expression to foster periodontal bone regeneration. This dynamic hydrogel system with MOFs, shows promise as a potential therapeutic avenue for addressing the challenges in bone regeneration in periodontitis.

Percutaneous versus traditional open approaches for the treatment of thoracolumbar fractures in patients without neurologic deficits: a meta-analysis of 35 cohort studies.

At present, percutaneous surgery is widely used to treat thoracolumbar fractures. However, the actual safety, feasibility, and effectiveness of percutaneous surgery are not clear. Through systematic review and meta-analysis, we compared the efficacies of percutaneous pedicle screw fixation and open pedicle screw fixation in the treatment of thoracolumbar fractures without nerve root symptoms. We systematically searched the PubMed, Embase, and Cochrane libraries for articles published on or before June 2023. All results were evaluated by standard methods recommended for meta-analysis, continuous data were expressed by standard mean differences (SMDs), and binary variables were analyzed by odds ratios (ORs) and 95% confidence intervals (95% CIs). We also explored the main sources of heterogeneity and the stability of the results through sensitivity analysis, Begg's funnel plots, and Egger's test. Thirty-five cohort studies with a total of 3039 patients were included. The study found that patients who undergo percutaneous approaches have less intraoperative blood loss (IBL), shorter length of hospital stay (LOS), shorter operation time, and shorter incision. Moreover, percutaneous approaches had more advantages in terms of visual analog scale (VAS) scores, Oswestry Disability Index (ODI) scores, and infection rates. However, there was no significant difference in anterior vertebral body height (AVB), Cobb angle (CA), or screw errors between the two groups. In the long run, the clinical and surgical results of the percutaneous approach are better than those of the open approach, but the radiological results of both operations do not seem to show an advantage for any specific approach. Because of publication bias and heterogeneity, our findings must be interpreted with caution. However, this paper will provide some support for clinicians to choose suitable surgical methods for the treatment of thoracolumbar fractures.

Anti-inflammatory cerium-containing nano-scaled mesoporous bioactive glass for promoting regenerative capability of dental pulp cells.

AIMS: This study aimed to investigate the anti-inflammatory and odontoblastic effects of cerium-containing mesoporous bioactive glass nanoparticles (Ce-MBGNs) on dental pulp cells as novel pulp-capping agents. METHODOLOGY: Ce-MBGNs were synthesized using a post-impregnation strategy based on the antioxidant properties of Ce ions and proposed the first use of Ce-MBGNs for pulp-capping application. The biocompatibility of Ce-MBGNs was analysed using the CCK-8 assay and apoptosis detection. Additionally, the reactive oxygen species (ROS) scavenging ability of Ce-MBGNs was measured using the 2,7-Dichlorofuorescin Diacetate (DCFH-DA) probe. The anti-inflammatory effect of Ce-MBGNs on THP-1 cells was further investigated using flow cytometry and quantitative real-time polymerase chain reaction (RT-qPCR). Moreover, the effect of Ce-MBGNs on the odontoblastic differentiation of the dental pulp cells (DPCs) was assessed by combined scratch assays, RT-qPCR, western blotting, immunocytochemistry, Alizarin Red S staining and tissue-nonspecific alkaline phosphatase staining. Analytically, the secretions of tumour necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were detected with enzyme-linked immunosorbent assay (ELISA). RESULTS: Ce-MBGNs were confirmed to effectively scavenge ROS in THP-1-derived macrophages and DPCs. Flow cytometry and RT-qPCR assays revealed that Ce-MBGNs significantly inhibited the M1 polarization of macrophages (Mφ). Furthermore, the protein levels of TNF-α and IL-1ß were downregulated in THP-1-derived macrophages after stimulation with Ce-MBGNs. With a step-forward virtue of promoting the odontoblastic differentiation of DPCs, we further confirmed that Ce-MBGNs could regulate the formation of a conductive immune microenvironment with respect to tissue repair in DPCs, which was mediated by macrophages. CONCLUSIONS: Ce-MBGNs protected cells from self-produced oxidative damage and exhibited excellent immunomodulatory and odontoblastic differentiation effects on DPCs. As a pulp-capping agent, this novel biomaterial can exert anti-inflammatory effects and promote restorative dentine regeneration in clinical treatment. We believe that this study will stimulate further correlative research on the development of advanced pulp-capping agents.

The bidirectional relationship between peer relationships and bullying: Evidence from cross-lagged analyses among Chinese children.

BACKGROUND: In the digital age, bullying manifests in two distinct forms: traditional bullying and cyberbullying. Children's peer relationships are important predictors of bullying, and bullying in turn predicts peer relationships. However, few researchers have noted the bidirectional relationship between peer relationships and bullying. METHODS: The present study used a two-wave cross-lagged longitudinal design to fill this gap. The potential sex differences were also examined in this relationship. The sample consisted of 527 Chinese children aged 8 to 12 years (M = 9.69, SD = .96; 53.5% female). Participants completed peer nominations for peer acceptance, peer rejection and social dominance, as well as self-reports of traditional bullying and cyberbullying. RESULTS: Results showed that peer rejection at the first time point (T1) significantly and positively predicted traditional bullying perpetration, cyberbullying perpetration and cyberbullying victimization at the second time point (T2). Traditional bullying victimization at T1 significantly and negatively predicted peer acceptance and social dominance at T2. The results also revealed significant male and female differences. For instance, among boys, peer acceptance at T1 significantly and negatively predicted cyberbullying victimization at T2. In contrast, this relationship was not observed among girls. The present findings have important implications for understanding the cyclical relationship between peer relationships and bullying and providing practical guidance for improving peer relationships and reducing bullying.

Self-Powered Disinfection Using Triboelectric, Conductive Wires of Metal-Organic Frameworks.

Efficient water disinfection is vitally needed in rural and disaster-stricken areas lacking power supplies. However, conventional water disinfection methods strongly rely on external chemical input and reliable electricity. Herein, we present a self-powered water disinfection system using synergistic hydrogen peroxide (H2O2) assisted electroporation mechanisms driven by triboelectric nanogenerators (TENGs) that harvest electricity from the flow of water. The flow-driven TENG, assisted by power management systems, generates a controlled output with aimed voltages to drive a conductive metal-organic framework nanowire array for effective H2O2 generation and electroporation. The injured bacteria caused by electroporation can be further damaged by facile diffused H2O2 molecules at high throughput. A self-powered disinfection prototype enables complete disinfection (>99.9999% removal) over a wide range of flows up to 3.0 × 104 L/(m2 h) with low water flow thresholds (200 mL/min; ∼20 rpm). This rapid, self-powered water disinfection method is promising for pathogen control.

Implication of lncRNA MSTRG.81401 in Hippocampal Pyroptosis Induced by P2X7 Receptor in Type 2 Diabetic Rats with Neuropathic Pain Combined with Depression.

Major depressive disorder (MDD) is a common complication of diabetes and is often observed alongside diabetic neuropathic pain (DNP) as a comorbidity in diabetic patients. Long non-coding RNA (lncRNA) plays an important role in various pathophysiological processes. The P2X7 receptor is responsible for triggering inflammatory responses, such as pyroptosis, linked to pain and depression. The aim of this study was to investigate the effect of lncRNA MSTRG.81401 on hippocampal pyroptosis induced by the P2X7 receptor in diabetic rats with DNP combined with MDD (DNP + MDD). Our results showed that the expression of lncRNA MSTRG.81401 was significantly elevated in the hippocampus of DNP + MDD rats compared with the control group. Following the administration of shRNA targeting lncRNA MSTRG.81401, a notable elevation in mechanical and thermal pain thresholds was observed in rats with comorbid DNP and MDD. Additionally, significant improvements in depression-like behaviors were evident in the open-field test (OFT), sucrose preference test (SPT), and forced swim test (FST). In the DNP + MDD rats, elevated levels in hippocampal P2X7 receptor mRNA and protein were observed, along with increased co-expression of P2X7 and the astrocytic marker glial fibrillary acidic protein (GFAP). Meanwhile, in DNP + MDD rats, the heightened mRNA expression of NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), pyroptosis-related protein Gasdermin D (GSDMD), caspase-1, IL-1ß, IL-18, and TNF-α was detected, in addition to increased serum levels of IL-1ß, IL-18 and TNF-α. After shRNA treatment with lncRNA MSTRG.81401, the above abnormal changes in indicators for pyroptosis and inflammation were improved. Therefore, our study demonstrates that shRNA of lncRNA MSTRG.81401 can alleviate the pain and depression-like behaviors in diabetic rats associated with the comorbidity of DNP and MDD by inhibiting the hippocampal P2X7 receptor-mediated pyroptosis pathway and pro-inflammatory responses. This suggests that the P2X7R/NLRP3/caspase-1 implicated pyroptosis and inflammatory scenario may serve as a potential target for the management of comorbid DNP and MDD in diabetes.

The comprehension of double negation in Chinese children with reading difficulties.

This study investigated the processing of double negation in Chinese children with reading difficulties. The comprehension of Mandarin affirmative, single negative and double negative sentences was tested with Chinese young poor readers and typical readers, using a sentence-picture verification task. Results showed that double negative sentences were most difficult to process for both groups; the poor readers performed significantly worse than the typical readers in comprehending double negative sentences, while no difference between the two groups was observed in comprehending affirmative and single negative sentences. Besides, morphological awareness correlated with the comprehension of double negative and single negative sentences in poor readers, while this correlation did not emerge with typical readers. Overall, our results suggest that children with reading difficulties experienced great processing difficulty in double negation, confirming that reading disorders are also characterised by oral language difficulties, in particular in the comprehension of sentences requiring high processing costs.

Gas Kinetic Scheme Coupled with High-Speed Modifications for Hypersonic Transition Flow Simulations.

The issue of hypersonic boundary layer transition prediction is a critical aerodynamic concern that must be addressed during the aerodynamic design process of high-speed vehicles. In this context, we propose an advanced mesoscopic method that couples the gas kinetic scheme (GKS) with the Langtry-Menter transition model, including its three high-speed modification methods, tailored for accurate predictions of high-speed transition flows. The new method incorporates the turbulent kinetic energy term into the Maxwellian velocity distribution function, and it couples the effects of high-speed modifications on turbulent kinetic energy within the computational framework of the GKS solver. This integration elevates both the transition model and its high-speed enhancements to the mesoscopic level, enhancing the method's predictive capability. The GKS-coupled mesoscopic method is validated through a series of test cases, including supersonic flat plate simulation, multiple hypersonic cone cases, the Hypersonic International Flight Research Experimentation (HIFiRE)-1 flight test, and the HIFiRE-5 case. The computational results obtained from these cases exhibit favorable agreement with experimental data. In comparison with the conventional Godunov method, the new approach encompasses a broader range of physical mechanisms, yielding computational results that closely align with the true physical phenomena and marking a notable elevation in computational fidelity and accuracy. This innovative method potentially satisfies the compelling demand for developing a precise and rapid method for predicting hypersonic boundary layer transition, which can be readily used in engineering applications.

Hepatocyte-specific Mas activation enhances lipophagy and fatty acid oxidation to protect against acetaminophen-induced hepatotoxicity in mice.

BACKGROUND & AIMS: Acetaminophen (APAP) is the most common cause of drug-induced liver injury (DILI); however, treatment options are limited. Mas is a G protein-coupled receptor whose role in APAP-induced hepatotoxicity has not yet been examined. METHODS: Intrahepatic Mas expression was determined in both human and mouse DILI models. Mas1-/-, AlbcreMas1f/f, Ppara-/-, Mas1-/-Ppara-/- and wild-type mice were challenged with APAP for the in vivo analyses of Mas-AKT-FOXO1 axis-dependent lipophagy and fatty acid oxidation (FAO), using pharmacological compounds and genetic tools. Liver samples were collected for RNA-sequencing, proteomics, metabolomics, lipidomics, and metabolic flux analysis. Live-imaging of liver and histological, biochemical, and molecular studies were performed to evaluate APAP-induced hepatotoxicity in mice. Primary hepatocytes and hepatic cell lines were exposed to APAP for in vitro analysis. RESULTS: Intrahepatic Mas expression was significantly upregulated in human and mouse DILI models. Mice with systemic, liver-specific, or hepatocyte-specific Mas1 deficiency were vulnerable to APAP-induced hepatotoxicity. They exhibited substantially impaired lipophagy and downstream FAO, which was accompanied by the activation of AKT and suppression of FOXO1. In addition, the prophylactic activation of Mas conferred strong protection against APAP challenge in mice, with remarkably enhanced lipophagy and FAO dependent on the AKT-FOXO1 axis. Moreover, the protective effects of AVE0991 were substantially diminished by the inhibition of either lipophagy or FAO. CONCLUSIONS: The activation of Mas on hepatocytes enhanced AKT-FOXO1-dependent lipophagy and downstream FAO, protecting mice from APAP-induced hepatotoxicity and indicating that hepatocyte-specific Mas might be a novel therapeutic target for DILI. IMPACT AND IMPLICATIONS: Mas signalling arises as a novel therapeutic target for patients with APAP-induced liver injury. The Mas-AKT/FOXO1-fatty acid degradation pathway could be critical for the development of treatment strategies for APAP overdose. When Mas signalling is targeted, the extent of liver injury should be considered at the time of administration. These findings obtained from APAP-challenged mice still need to be confirmed in a clinical context.

Acetamide- or Formamide-Assisted In Situ Approach to Carbon-Rich or Nitrogen-Deficient Graphitic Carbon Nitride for Notably Enhanced Visible-Light Photocatalytic Redox Performance.

Acetamide- or formamide-assisted in situ strategy is designed to synthesize carbon atom self-doped g-C3 N4 (AHCNx ) or nitrogen vacancy-modified g-C3 N4 (FHCNx ). Different from the direct copolymerization route that suffers from the problem of mismatched physical properties of acetamide (or formamide) with urea, the synthesis of AHCNx (or FHCNx ) starts from a crucial preorganization step of acetamide (or formamide) with urea via freeze drying-hydrothermal treatment so that the chemical structures as well as C-doping level in AHCNx and N-vacancy concentration in FHCNx can be precisely regulated. By using various structural characterization methods, well-defined AHCNx and FHCNx structures are proposed. At the optimal C-doping level in AHCNx or N-vacancy concentration in FHCNx , both AHCNx and FHCNx exhibit remarkably improved visible-light photocatalytic performance in oxidation of emerging organic pollutants (acetaminophen and methylparaben) and reduction of proton to H2 in comparison of unmodified g-C3 N4 . Combination of the experimental results with theoretical calculations, it is confirmed that AHCNx and FHCNx show different charge separation and transfer mechanisms, while the enhanced visible-light harvesting capacity and the localized charge distributions on HOMO and LUMO are responsible for this excellent photocatalytic redox performance of AHCNx and FHCNx .